Inflammation serves an important role in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. Fragments of endogenous damaged‑associated molecular patterns, recently identified as mitochondrial DNA (mtDNA), have been proven to be a potent pro‑inflammatory mediator. Epigallocatechin‑3‑gallate (EGCG) is able to regulate the expression levels of a series of inflammatory cytokines. However, the involvement of endogenous mtDNA in EGCG‑regulated inflammatory activities in the context of myocardial I/R injury remains to be elucidated. The present study was designed to investigate the role of mtDNA in EGCG‑mediated myocardial protection in a rat I/R model. Significant positive correlations between elevated plasma mtDNA copy numbers and the expression levels of tumor necrosis factor (TNF) and interleukins (IL)‑6 and ‑8 were observed in the myocardial tissue following an I/R injury (P<0.05). However, EGCG administered prior to reperfusion was able to effectively downregulate the expression levels of plasma mtDNA, TNF and IL‑6 and ‑8 in the myocardial tissue following an I/R injury (P<0.05). Limited infarct size, reduced severity of myocardial injury and decreased incidence of ventricular arrhythmia were observed in the EGCG‑treated group. However, the beneficial effects of EGCG in preventing myocardial I/R injury may be eliminated by a specific phosphoinositide‑3‑kinase (PI3K) inhibitor. These results suggested that EGCG‑mediated cardioprotective effects may be achieved by inhibiting the release of mtDNA from damaged mitochondria and that this protection was at least in part dependent on the PI3K/RAC‑α serine/threonine‑protein kinase associated signaling pathway.

HTX-011 is an extended-release, dual-acting local anesthetic consisting of bupivacaine and low-dose meloxicam in a novel polymer that is administered by needle-free application during surgery. The active ingredients are released from the polymer by controlled diffusion over 72 hours. This phase 2b, double-blind, placebo-controlled and active-controlled trial enrolled patients undergoing primary unilateral total knee arthroplasty under general anesthesia. Two hundred thirty-two patients were randomized into 4 groups: HTX-011 400 mg bupivacaine/12 mg meloxicam, applied without a needle into the surgical site, the same dose of HTX-011 with a separate 50 mg ropivacaine injection into the posterior capsule, bupivacaine hydrochloride (HCl) 125 mg injection, and saline placebo injection. Only opioids were permitted for postoperative pain rescue. Primary and key secondary endpoints were mean area under the curve of pain intensity scores over 48 hours and 72 hours, respectively, for HTX-011 groups vs placebo. Both HTX-011 groups had significantly reduced mean pain intensity vs placebo through 48 and 72 hours (both P < .001). Ropivacaine added a small initial benefit in the first 12 hours. Both HTX-011 groups also had decreased mean pain intensity vs bupivacaine HCl alone through 48 and 72 hours (P < .05). The HTX-011 groups had significantly earlier discharge readiness along with lower opioid consumption through 72 hours. HTX-011 alone or with ropivacaine was well-tolerated with a safety profile similar to controls. Needle-free application of HTX-011 400 mg bupivacaine/12 mg meloxicam provided superior pain reduction through 72 hours after total knee arthroplasty compared with placebo and bupivacaine HCl alone.

Background: Intestinal barrier dysfunction would lead to a rigorous inflammatory reaction due to the translocation of intestinal lumen-derived bacteria and endotoxins. The aim of the present study was to investigate whether intestinal barrier dysfunction occurs in patients with acute Stanford type A aortic dissection (ATAAD) and to determine its potential relationship with the plasma levels of several inflammatory biomarkers in the progression of ATAAD. Design and Methods: Serum samples from a total of 46 patients with ATAAD and 36 healthy volunteers were prospectively collected and analyzed. The serum levels of diamine oxidase (DAO), lactate dehydrogenase (LDH), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and C-reactive protein (CRP) were measured using colorimetric assay, enzyme-linked immunosorbent assay, and immunoturbidimetric assay. Results: Serum levels of DAO, LDH, IL-6, TNF-α, and CRP in patients with ATAAD were significantly higher than those in healthy participants. A significantly positive correlation between DAO activity and IL-6 ( r = .56, P < .001), TNF-α ( r = .63, P < .001), and CRP ( r = .53, P < .001) was observed. Moreover, the activity of DAO correlated negatively with the Pao₂/fraction of inspired oxygen (Fio₂) ratio ( r = −.39, P = .007). Conclusions: Intestinal barrier dysfunction, reflected by an increased level of serum DAO, may play an important role in the development of systemic inflammatory responses in patients with ATAAD. Therefore, strategies of preserving a normal intestinal barrier function may open new horizons in the treatment of inflammation-related adverse events in the setting of ATAAD.

To investigate the time-dependent changes in plasma levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α in patients with type A aortic dissection (TAAD) who received unoptimal medical management since the onset of dissections. Plasma levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α were detected by ELISA and immuno-turbidimetric assay in 92 TAAD patients at hospital admission. Blood samples from 78 patients with uncontrolled hypertension and 82 healthy volunteers were also analyzed as controls. The occurrence of TAAD-related complication and its relationship with the plasma levels of these inflammatory biomarkers was also investigated. The concentrations of inflammatory mediators were significant higher in TAAD than those in the uncontrolled hypertension and the healthy group. The time to peak plasma level of IL-6.and TNF-α was shorter than that of CRP in TAAD group. In the TAAD group, 51 patients suffered TAAD-related complications, and their plasma level of CRP was significantly higher than that in patients without TAAD-related complications (94.5 ± 58.8 mg/L versus 47.4 ± 47.8 mg/L, p < 0.001). Also, CRP levels strongly correlated with the value of PaO2/FiO2 ratio (r = −0.69, p < 0.001) and creatinine (r = 0.60, p < 0.001). The time to the peak level of CRP was shorter and the duration of persistently high CRP level was longer in the complication group than those in the complication-free group. Elevated and persistently high levels of plasma CRP, IL-6 and TNF-α were associated with progressively development of the TAAD. The changing pattern of CRP might be a marker for diagnosis and prophylactic treatment of complications. Our findings suggested a critical role of the inflammation in the progression of dissection and TAAD-related complications.

The clinical presentation and natural courses in acute non-A-non-B aortic dissection (AD) are quite different from classical acute type A or type B AD, and the benefit of hybrid technique for this clinical scenario has not been validated. By using computational fluid dynamics (CFD) analysis, we aim to investigate a series of hemodynamic-related changes in aortic morphology in a patient who underwent type I hybrid arch repair (HAR). Computed tomographic angiographies (preoperative, one week, one month and one year after HAR) of a 52-year old male patient with arch-entry type acute non-A-non-B dissection were collected. Three-dimensional models were reconstructed by using an image processing package Mimics (materialize). Morphological and hemodynamic parameters of aorta and its branch vessels were analysed. Post-operatively, the false lumen index (FLI) gradually decreased from 2.02 to 0.38 and the curvature of the aortic arch was also reduced. However, the aortic arch lengthened and the diameter of the distal abdominal aorta expanded. In addition, the blood flow gradually became organised and the pressure in the true lumen (TL) increased over time and eventually approximated the pressure in the false lumen (FL). Moreover, the region of the abnormal wall shear stress (WSS) in the TL progressively decreased while the WSS in most areas of the FL remained below 4 dyne/cm². The blood supply to most of the aortic branches returned to normal at the one-year follow-up. Type I HAR is an effective procedure for patients with acute non-A-non-B aortic dissection in terms of restoring normal blood flow in TL and facilitating positive remodeling of distal aorta. Long-term surveillance and follow-up is mandatory.

Background: A floating thrombus in an ascending aorta with normal morphology is very rare, but when it does occur, it may induce a systemic embolism or fatal stroke. The pathophysiological mechanisms of aortic mural thrombi remain unclear, and there is no consensus regarding therapeutic recommendations. Case presentation: We report a 49-year-old male who presented with chest discomfort for 5 days and was admitted to our emergency unit. A contrast-enhanced computed tomography angiography (CTA) surprisingly demonstrated a large filling defect suggestive of a thrombus in his otherwise healthy distal ascending aorta. Surgical resection of the mass and attachment site was performed. Histological examination confirmed that the mass was a thrombus, but the cause of the thrombus formation was unknown. Conclusions: floating aortic thrombi are rare, and they are prone to break off, thus carrying a potential risk for embolic events with catastrophic consequences. Surgical resection, both of the aortic thrombus and attachment site, as well as postoperative anticoagulant administration, are standard treatments.